Anti-CD20 antibody therapy and susceptibility to Pneumocystis pneumonia.
Anti-CD20 antibody therapy has been a useful medication for managing non-Hodgkin's lymphoma as well as autoimmune diseases characterized by autoantibody generation. CD20 is expressed during most developmental stages of B lymphocytes; thus, CD20 depletion leads to B-lymphocyte deficiency. As the drug has become more widely used, there has been an increase in the number of case reports of patients developing Pneumocystis pneumonia. The role of anti-CD20 in Pneumocystis jirovecii infection is under debate due to the fact that most patients receiving it are on a regimen of multiple immunosuppressive medications. To address the specific role of CD20 depletion in host immunity against Pneumocystis, we examined a murine anti-CD20 depleting antibody. We demonstrated that anti-CD20 alone is permissive for Pneumocystis infection and that anti-CD20 impairs components of type II immunity, such as production of interleukin-4 (IL-4), IL-5, and IL-13 by whole-lung cells, in response to Pneumocystis murina. We also demonstrated that CD4(+) T cells from mice treated with anti-CD20 during Pneumocystis infection are incapable of mounting a protective immune response when transferred into Rag1(-/-) mice. Thus, CD20(+) cells are critical for generating protective CD4(+) T-cell immune responses against this organism.
Department of Immunology, University of Pittsburgh School of Medicine (UPSOM), Pittsburgh, Pennsylvania, USA Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.
Waleed
W
Elsegeiny
Department of Immunology, University of Pittsburgh School of Medicine (UPSOM), Pittsburgh, Pennsylvania, USA Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.
Taylor
T
Eddens
Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.
Kong
K
Chen
Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA jay.kolls@chp.edu.
Jay K
JK
Kolls
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D007155:Immunologic Factors / Q000009:adverse effects* / Q000627:therapeutic use; D008810:Mice, Inbred C57BL; D011010:Pneumocystis / Q000276:immunology; D011020:Pneumonia, Pneumocystis / Q000139:chemically induced* / Q000276:immunology*; D000069283:Rituximab / Q000009:adverse effects* / Q000627:therapeutic use
D007155:Immunologic Factors; D000069283:Rituximab