Lymphoproliferative disorders are a set of disorders characterized by the abnormal proliferation of lymphocytes into a monoclonal lymphocytosis. The two major types of lymphocytes are B cells and T cells, which are derived from pluripotent hematopoetic stem cells in the bone marrow. Individuals who have some sort of dysfunction with their immune system are susceptible to develop a lymphoproliferative disorder because when any of the numerous control points of the immune system become dysfunctional, immunodeficiency or deregulation of lymphocytes is more likely to occur. There are several inherited gene mutations that have been identified to cause lymphoproliferative disorders; however, there are also acquired and iatrogenic causes.

Lymphoproliferative disorders (LPDs) refer to several conditions in which lymphocytes are produced in excessive quantities. They typically occur in people who have a compromised immune system. They are sometimes equated with "immunoproliferative disorders", but technically lymphoproliferative disorders are a subset of immunoproliferative disorders, along with hypergammaglobulinemia and paraproteinemias.

In terms of the "normal" mechanism of T cell we find that it is a type of white blood cell that has an important role in immunity, and is made from thymocytes One sees in the "partial" disorder of T cells that happen due to cell signaling defects, are usually caused by hypomorphic gene defects Generally, (micro)deletion of 22Q11.2 is the most often seen.

Presentations differ among causes, but T cell insufficiency generally manifests as unusually severe common viral infections (respiratory syncytial virus, rotavirus), diarrhea, and eczematous or erythrodermatous rashes. Failure to thrive and cachexia are later signs of a T-cell deficiency.

Persons afflicted with X-SCID often have infections very early in life, before three months of age. This occurs due to the decreased amount of immunoglobulin G (IgG) levels in the infant during the three-month stage. This is followed by viral infections such as pneumonitis, an inflammation of the lung which produces common symptoms such as cough, fever, chills, and shortness of breath. A telltale sign of X-SCID is candidiasis, a type of fungal infection caused by "Candida albicans". Candidiasis involves moist areas of the body such as skin, the mouth, respiratory tract, and vagina; symptoms of oral candidiasis include difficulty in swallowing, pain on swallowing and oral lesions. Recurrent eczema-like rashes are also a common symptom. Other common infections experienced by individuals with X-SCID include diarrhea, sepsis, and otitis media. Some other common symptoms that are experienced by X-SCID patients include failure to thrive, gut problems, skin problems, and muscle hypotonia.

In some patients symptoms may not appear for the first six months after birth. This is likely due to passive immunity received from the mother in order to protect the baby from infections until the newborn is able to make its own antibodies. As a result, there can be a silent period where the baby displays no symptoms of X-SCID followed by the development of frequent infections.

A lymphocyte is one of the subtypes of white blood cell in a vertebrate's immune system. Lymphocytes include natural killer cells (Phagocytes) (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adaptive immunity), and B cells (for humoral, antibody-driven adaptive immunity). They are the main type of cell found in lymph, which prompted the name "lymphocyte".

A T cell, or T lymphocyte, is a type of lymphocyte (a subtype of white blood cell) that plays a central role in cell-mediated immunity. T cells can be distinguished from other lymphocytes, such as B cells and natural killer cells, by the presence of a T-cell receptor on the cell surface. They are called "T cells" because they mature in the thymus from thymocytes (although some also mature in the tonsils). The several subsets of T cells each have a distinct function. The majority of human T cells rearrange their alpha and beta chains on the cell receptor and are termed alpha beta T cells (αβ T cells) and are part of the adaptive immune system. Specialized gamma delta T cells, (a small minority of T cells in the human body, more frequent in ruminants), have invariant T-cell receptors with limited diversity, that can effectively present antigens to other T cells and are considered to be part of the innate immune system.

The typical patient with lymphocyte-variant hypereosinophilia presents with an extended history of hypereosinophilia and cutaneous allergy-like symptoms. Skin symptoms, which occur in >75% of patients, include erythroderma, pruritis, eczema, Poikiloderma, urticarial, and episodic angioedema. The symptom of episodic angioedema in lymphocyte-variant hypereosinophilia resembles that occurring in Gleich's syndrome, a rare disease that is accompanied by secondary hypereosinophilia plus a sub-population of CD3(-), CD4(+) T cells and therefore proposed, at least in many patients, a subtype of lymphocyte-variant hypereosiophilia. Biopsies of these erythroderma and eczema skin lesions find prominent accumulations of eosinophils. Other presentations include; a) lymphadenopathy occurring in ~60% of patients; b) eosinophil infiltrations in lung similar to, and often diagnosed as, eosinophilic pneumonia, occurring in ~20% of patients; c) episodic angioedema-related gastrointestinal symptoms that are sometimes similar to symptoms of the irritable bowel syndrome occurring in ~20% of patients; d) rheumatologic manifestations of inflammatory arthralgias in ~20% of patients; and e) splenomegaly occurring in ~10% of patients. Cardiovascular complications such as various types of heart damage (see above History section) and vascular injuries due to eosinophil infiltration and eosinophil-induced thrombosis are often critical components of persistent hypereosinohilia syndromes; These complications are not a prominent component of lymphocyte-variant hypereosionophilia, occurring in <10% of patients.

Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer cells. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self and foreign lipids and glycolipids. They constitute only approximately 0.1% of all blood T cells. Natural killer T cells should not be confused with natural killer cells.

Lymphocyte-variant hypereosinophila, also termed lymphocyte variant eosinophilia, is a rare disorder in which eosinophilia or hypereosinophilia (i.e. a large or extremely large increase in the number of eosinophils in the blood circulation) is caused by aberrant population of lymphocytes. These aberrant lymphocytes function abnormally by stimulating the proliferation and maturation of bone marrow eosinophil-precursor cells termed colony forming unit-Eosinophils or CFU-Eos.

The overly stimulated CFU-Eos cells mature to apparently normal eosinophils, enter the circulation, and may accumulate in, and severely damage, various tissues. The disorder is usually indolent or slowly progressive but may proceed to a leukemic phase and at this phases is sometimes classified as acute eosinophilic leukemia. Hence, lymphocyte-variant hypereosinophilia can be regarded as a precancerous disease.

The order merits therapeutic intervention to avoid or reduce eosinophil-induced tissue injury and to treat its leukemic phase. The latter phase of the disease is aggressive and typically responds relatively poorly to anti-leukemia chemotherapeutic drug regimens.

X-linked severe combined immunodeficiency (X-SCID) is an immunodeficiency disorder in which the body produces very few T cells and NK cells. In the absence of T cell help, B cells become defective. It is an x-linked recessive trait, stemming from a mutated (abnormal) version of the IL2-RG gene located at xq13.1 on the X-chromosome, which is shared between receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.

The three major types of lymphocyte are T cells, B cells and natural killer (NK) cells. Lymphocytes can be identified by their large nucleus.

Cytokine-induced killer cells or CIK cells are a group of immune effector cells featuring a mixed T- and natural killer (NK) cell-like phenotype. They are generated by ex vivo incubation of human peripheral blood mononuclear cells (PBMC) or cord blood mononuclear cells with interferon-gamma (IFN-γ), anti-CD3 antibody, recombinant human interleukin (IL-) 1 and recombinant human interleukin (IL)-2.

Typically, immune cells detect major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing lysis or apoptosis. However, CIK cells have the ability to recognize infected or even malignant cells in the absence of antibodies and MHC, allowing for a fast and unbiased immune reaction. This is of particular importance as harmful cells that are missing MHC markers cannot be tracked and attacked by other immune cells, such as T-lymphocytes. As a special feature, terminally differentiated CD3+CD56+ CIK cells possess the capacity for both MHC-restricted and MHC-unrestricted anti-tumor cytotoxicity.

These properties, inter alia, rendered CIK cells attractive as a potential therapy for cancer and viral infections.

This disease is known for an indolent clinical course and incidental discovery. The most common physical finding is moderate splenomegaly. B symptoms are seen in a third of cases, and recurrent infections due to the associated neutropenia are seen in almost half of cases.

Rheumatoid arthritis is commonly observed in people with T-LGLL, leading to a clinical presentation similar to Felty's syndrome. Signs and symptoms of anemia are commonly found, due to the association between T-LGLL and erythroid hypoplasia.

The leukemic cells of T-LGLL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.

In some cases, lymphocytopenia can be further classified according to which kind of lymphocytes are reduced. If all three kinds of lymphocytes are suppressed, then the term is used without further qualification.

- In T lymphocytopenia, there are too few T lymphocytes, but normal numbers of other lymphocytes. It causes, and manifests as, a T cell deficiency. This is usually caused by HIV infection (resulting in AIDS), but may be Idiopathic CD4+ lymphocytopenia (ICL), which is a very rare heterogeneous disorder defined by CD4+ T-cell counts below 300 cells/μL in the absence of any known immune deficiency condition, such as human immunodeficiency virus (HIV) infection or chemotherapy.

- In B lymphocytopenia, there are too few B lymphocytes, but possibly normal numbers of other lymphocytes. It causes, and manifests as, a humoral immune deficiency. This is usually caused by medications that suppress the immune system.

- In NK lymphocytopenia, there are too few natural killer cells, but normal numbers of other lymphocytes. This is very rare.

A naïve T cell (T0 cell) is a T cell that has differentiated in bone marrow, and successfully undergone the positive and negative processes of central selection in the thymus. Among these are the naïve forms of helper T cells (CD4+) and cytotoxic T cells (CD8+). A naïve T cell is considered mature and, unlike activated or memory T cells, has not encountered its cognate antigen within the periphery.

Lymphocytopenia, or lymphopenia, is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. The opposite is lymphocytosis, which refers to an excessive level of lymphocytes.

Lymphocytopenia may be present as part of a pancytopenia, when the total numbers of all types of blood cells are reduced.

Certain malignancies cause a secondary eosinophilia or, less commonly, hypereosinophilia. These increases in blood eosinophils appear due to the release of stimulatory cytokines or invasion of the bone marrow and thereby irritation of resident eosinophils or their precursors. Malignancies associated with these effects include gastric, colorectal, lung, bladder, and thyroid cancers, as well as squamous cell cancers of the cervix, vagina, penis, skin, and nasopharyrnx. Some hematological malignancies are likewise associated with secondary rises in blood eosinophil counts; these include Hodgkin disease, certain T-cell lymphomas, acute myeloid leukemia , the myelodysplastic syndromes, many cases of systemic mastocytosis, chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, myelofibrosis, chronic myelomonocytic leukemia, and certain cases of T-lymphoblastic leukemia/lymphoma-associated or myelodysplastic–myeloproliferative syndrome-associated eosinophilias.

The category of effector T cell is a broad one that includes various T cell types that actively respond to a stimulus, such as co-stimulation. This includes helper, killer, regulatory, and potentially other T cell types.

The regulatory T cells (Tregs ), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Tregs are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. Tregs express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same lineage as naïve CD4 cells. Because effector T cells also express CD4 and CD25, Tregs are very difficult to effectively discern from effector CD4+, making them difficult to study. Recent research has found that the cytokine TGFβ is essential for Tregs to differentiate from naïve CD4+ cells and is important in maintaining Treg homeostasis.

Mouse models have suggested that modulation of Tregs can treat autoimmune disease and cancer and can facilitate organ transplantation. Their implications for cancer are complicated. Tregs tend to be upregulated in individuals with cancer, and they seem to be recruited to the site of many tumors. Studies in both humans and animal models have implicated that high numbers of Tregs in the tumor microenvironment is indicative of a poor prognosis, and Tregs are thought to suppress tumor immunity, thus hindering the body's innate ability to control the growth of cancerous cells. Recent immunotherapy research is studying how regulation of T cells could possibly be utilized in the treatment of cancer.

The term "NK T cells" was first used in mice to define a subset of T cells that expressed the natural killer (NK) cell-associated marker NK1.1 (CD161). It is now generally accepted that the term "NKT cells" refers to CD1d-restricted T cells, present in mice and humans, some of which coexpress a heavily biased, semi-invariant T-cell receptor and NK cell markers.

A wide range of drugs are known to cause hypereosinophilia or eosinophilia accompanied by an array of allergic symptoms. Rarely, these reactions are severe causing, for example, the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. While virtually any drug should be considered as a possible cause of these signs and symptoms, the following drugs and drug classes are some of the most frequently reported causes: penicillins, cephalosporins, dapsone, sulfonamides, carbamazepine, phenytoin, lamotrigine, valproic acid, nevirapine, efavirenz, and ibuprofen. These drugs may cause severely toxic reactions such as the DRESS syndrome. Other drugs and drug classes often reported to cause increased blood eosinophil levels accompanied by less severe (e.g. non-DRESS syndrome) symptoms include tetracyclins, doxycycline, linezolid, nitrofurantoin, metronidazole, carbamazepine, phenobarbital, lamotrigine, valproate, desipramine, amitriptyline, fluoxetine, piroxicam, diclofenac, ACE inhibitors, abacavir, nevirapine, ranitidine, cyclosporin, and hydrochlorothiazide.

The toxic oil syndrome is associated with hypereosinophilia/eosinophilia and systemic symptoms due to one or more contaminants in rapeseed oil and the Eosinophilia–myalgia syndrome, also associated with hypereosinophilia, appears due to trace contaminants in certain commercial batches of the amino acid, L-tryptophan.

B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system by secreting antibodies. Additionally, B cells present antigen (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines.

In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ. (The "B" from B cells comes from the name of this organ, where it was first discovered by Chang and Glick, and not from bone marrow as commonly believed).

B cells, unlike the other two classes of lymphocytes, T cells and natural killer cells, express B cell receptors (BCRs) on their cell membrane. BCRs allow the B cell to bind a specific antigen, against which it will initiate an antibody response.

Hyper IgM syndromes is a group of primary immune deficiency disorders characterized by defective CD40 signaling; "via" B cells affecting class switch recombination (CSR) and somatic hypermutation. Immunoglobulin (Ig) class switch recombination deficiencies are characterized by elevated serum Immunoglobulin M (IgM) levels and a considerable deficiency in Immunoglobulins G (IgG), A (IgA) and E (IgE). As a consequence, people with HIGM have decreased concentrations of serum IgG and IgA and normal or elevated IgM, leading to increased susceptibility to infections.