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What are the Immunophenotypic Features and Significance of gamma-delta T cells?

T-cells are divided in two subsets based on heterodimer surface receptor expression. These subsets are alpha-beta (αβ) and gamma-delta (γδ) T-cells. The majority of T-cells in peripheral blood (PB) are those of alpha-beta phenotype with fewer exhibiting gamma-delta phenotype (1-5% with an absolute range of 55 to 120 gamma-delta T-cells per microliter) (see A. Roden, et al). The gamma-delta T-cells are also seen in extramedullary tissue such as skin and gastrointestinal tract. The frequency of gamma-delta T-cells vary in PB samples from healthy individuals and may be affected by ethnic/genetic and environmental factors. In study by E. Esin et al; gamma-delta T-cells appeared to be more frequent in non-Japanese Asian and significantly lower in Swedish and Japanese healthy individuals. The gamma-delta T-cells may be increased in frequency in association with infection such as mycobacterial or viral, autoimmune/ connective tissue diseases, or immune suppression/ immune dysregulation, among others. Therefore, this T-cell subset appears to have critical role in the immune response to such disorders. The reactive gamma-delta T-cells are, by definition, positive for gamma-delta surface receptor and usually exhibit surface CD3 (occasionally brighter than expected) expression and negative CD4 and CD8 expression (double-negative); although occasionally CD8 may be partially expressed. In regard to pan-T-cell markers; these cells are usually positive for CD2, CD5, and CD7 but loss or decreased expression of CD5 and less frequently decreased expression of CD7 may be encountered. In this regard, the loss or decreased expression of CD5 is the most commonly seen immunophenotypic feature of the reactive gamma-delta T-cells (see examples). In addition, these cells are occasionally positive for CD56 or CD57 (see A. Roden, et al, and example 3). When gamma-delta T-cells are noted in increased frequencies in samples analyzed by flow cytometry (mainly PB samples), it is critical to recognize reactive nature of these cells and differentiate between reactive polyclonal expansion versus neoplastic monoclonal T-cell lymphoproliferative disorders of gamma-delta phenotype such as hepatosplenic T-cell lymphoma. Overall, gamma-delta T-cells have variable immunophenotypic features that may appear worrisome, especially in the context of flow cytometry work up for mature T-cell lymphoproliferative disorders. Therefore, it is critical to note the presence of this subset, address its frequency, recognize its unique immunophenotypic features, and correlate the flow cytometry immunophenotypic findings with those of the morphologic and clinical findings. REFERENCES 1. Esin S, et al. Different percentages of peripheral blood gamma delta + T cells in healthy individuals from different areas of the world. Scand J Immunol 1996, 43:593-6. 2. Dechanet J, et al. Major expansion of gammadelta T lymphocytes following cytomegalovirus infection in kidney allograft recipients. J Infect Dis 1999, 179:1-8. 3. McClanahan J, et al. Increased peripheral blood gamma delta T-cells in patients with lymphoid neoplasia: A diagnostic dilemma in flow cytometry. Cytometry 1999, 38:280-5. 4. Roden AC, et al. Immunophenotypic attributes of benign peripheral blood gamma-delta T cells and conditions associated with their increase. Arch Pathol Lab Med 2008, 132:1774-80.

Author: George Deeb, Andrea Illingworth, David Ng, Kim Le