Role of common gamma chain utilizing cytokines for immune reconstitution in HIV infection
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Role of common gamma chain utilizing cytokines for immune reconstitution in HIV infection Savita Pahwa
Published online: 21 June 2007 Humana Press Inc. 2007
Abstract Many cytokines that utilize the common gamma (Cc) chain signaling pathway, viz Interleukin (IL)-2, IL-15, and IL-7 are known to be important for inducing T cell maturation, proliferation, or survival. Untreated chronic HIV infection is associated with profound quantitative and qualitative deficiency of CD4 T cells, which is partially reversed following highly active antiretroviral therapy (HAART). A subset of patients, however, fail to recover CD4 T cells despite virologic suppression. The role of Cc chain cytokines in influencing immune reconstitution following potent antiretroviral therapy is discussed. Maturation markers (naı¨ve, central memory, effector memory, and effector), cytokine receptors IL-2Rb, Cc chain, IL-7Ra, IL-15Ra, and cytokine-induced proliferative responses of T cells in a cohort of HIV-infected pediatric patients and adults classified on the basis of immunologic and virologic response to antiretroviral therapy were examined. The studies indicated that patients had increased percentages of effector memory CD8+ T cells in comparison to healthy volunteers. While patients with partially controlled viremia and poor CD4 T cell reconstitution manifested poor proliferative responses to anti-CD3 or HIV gag antigen stimulation, proliferative responses to Cc chain utilizing cytokines IL-2, IL-7, and IL-15 were robust. Another Cc chain utilizing cytokine, IL-21 had no influence on cellular proliferation but enhanced perforin expression in effector CD8 T cells. Thus, cytokine receptor deficiencies may contribute to immune deficiency in HIV-infected patients, and Cc chain cytokines may play an important role in vivo in immune homeostasis in lymphopenic patients by maintaining the memory subsets of T cells in patients with CD4 T cell deficiency. Keywords HIV infection Immune deficiency Immune reconstitution Immune hemeostasis
Presented at the First Robert A Good Society Symposium, St. Petersburg, FL 2006 S. Pahwa (&) Miller School of Medicine, Department of Microbiology and Immunology, University of Miami, 1580 NW 10th Avenue, BCRI-712, Miami, FL 33136, USA e-mail: [email protected]
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Immunol Res (2007) 38:373–386
Introduction Much of our understanding of the clinical relevance of the ever-expanding family of cytokines that utilize the common gamma chain stems from patients with genetic disorders, so aptly coined by Dr Robert Good as ‘‘experiments of nature.’’ A glimpse into how interleukin-2, the earliest member of this family could impact human disease was in fact provided by patients with the disease phenotype of severe combined immune deficiency or SCID, who lacked the two arms of the immune system discovered by Dr Good [1]. Since its original phenotypic description, a variety of genetic causes for SCID have been identified. The most common form, X-linked SCID, is caused by mutations of the IL-2R gamma chain. The reason for
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