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Infection and Immunity, November 2009, p. 5090-5096, Vol. 77, No. 11
0019-9567/09/$08.00+0 doi:10.1128/IAI.00793-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Memory T-Cell Responses to Vibrio cholerae O1 Infection
Ana A. Weil,1,
Mohammad Arifuzzaman,1,
Taufiqur R. Bhuiyan,1
Regina C. LaRocque,2,3
Aaron M. Harris,1
Emily A. Kendall,1
Azim Hossain,1
Abdullah A. Tarique,1
Alaullah Sheikh,1
Fahima Chowdhury,1
Ashraful I. Khan,1
Farhan Murshed,2
Kenneth C. Parker,4
Kalyan K. Banerjee,5
Edward T. Ryan,2,3,6
Jason B. Harris,2,7,
Firdausi Qadri,1, and
Stephen B. Calderwood2,3,8*,
International Centre for Diarrheal Disease Research, Dhaka, Bangladesh,1 Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts,2 Department of Medicine, Harvard Medical School, Boston, Massachusetts,3 Virgin Instruments, Sudbury, Massachusetts,4 Division of Biochemistry, National Institute of Cholera and Enteric Diseases, Kolkata, India,5 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts,6 Department of Pediatrics, Harvard Medical School, Boston, Massachusetts,7 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts8
Received 15 July 2009/ Returned for modification 5 August 2009/ Accepted 13 August 2009
Vibrio cholerae O1 can cause diarrheal disease that may be life-threatening without treatment. Natural infection results in long-lasting protective immunity, but the role of T cells in this immune response has not been well characterized. In contrast, robust B-cell responses to V. cholerae infection have been observed. In particular, memory B-cell responses to T-cell-dependent antigens persist for at least 1 year, whereas responses to lipopolysaccharide, a T-cell-independent antigen, wane more rapidly after infection. We hypothesize that protective immunity is mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue, and T-cell responses may be required to generate and maintain durable memory B-cell responses. In this study, we examined B- and T-cell responses in patients with severe V. cholerae infection. Using the flow cytometric assay of the specific cell-mediated immune response in activated whole blood, we measured antigen-specific T-cell responses using V. cholerae antigens, including the toxin-coregulated pilus (TcpA), a V. cholerae membrane preparation, and the V. cholerae cytolysin/hemolysin (VCC) protein. Our results show that memory T-cell responses develop by day 7 after infection, a time prior to and concurrent with the development of B-cell responses. This suggests that T-cell responses to V. cholerae antigens may be important for the generation and stability of memory B-cell responses. The T-cell proliferative response to VCC was of a higher magnitude than responses observed to other V. cholerae antigens.
* Corresponding author. Mailing address: Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114. Phone: (617) 726-3811. Fax: (617) 726-7416. E-mail: scalderwood{at}partners.org
Published ahead of print on 24 August 2009.
A.A.W. and M.A. contributed equally as first authors for this work.
J.B.H., F.Q., and S.B.C. contributed equally as senior authors for this work.
Infection and Immunity, November 2009, p. 5090-5096, Vol. 77, No. 11
0019-9567/09/$08.00+0 doi:10.1128/IAI.00793-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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